1 Cardiovascular Department Chang Gung Memorial Hospital Linkou, Taoyuan Taiwan.
6 College of Medicine Chang Gung University Taoyuan Taiwan.
J Am Heart Assoc. 2019 Mar 5;8(5):e011112. doi: 10.1161/JAHA.118.011112.
Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients.
患有非瓣膜性心房颤动的肝硬化患者已被排除在有关预防中风的口服抗凝药物的随机临床试验之外。新型口服抗凝剂（NOACs）是否优于华法林用于这些患者仍不清楚。
本项全国性回顾性队列研究的数据来自于台湾全民健康保险研究数据库，共纳入了 2012 年 6 月 1 日至 2016 年 12 月 31 日期间服用阿哌沙班（n=171）、达比加群（n=535）、利伐沙班（n=732）或华法林（n=990）的 2428 例非瓣膜性心房颤动的肝硬化患者。我们使用基于倾向评分的稳定权重来平衡研究组之间的协变量。患者随访至发生事件或研究结束日期。NOAC 组（n=1438）在调整后其缺血性中风/全身性栓塞和颅内出血的风险与华法林组（n=990）相当。NOAC 组胃肠道出血（风险比：0.51 [95%CI，0.32-0.79]；P=0.0030）和所有主要出血（风险比：0.51 [95%CI，0.32-0.74]；P=0.0003）的风险显著低于华法林组。总体而言，90%（n=1290）的患者服用低剂量的 NOAC（阿哌沙班 2.5mg，每日两次；利伐沙班 10-15mg，每日一次；或达比加群 110mg，每日两次）。亚组分析表明，达比加群和利伐沙班的所有主要出血风险均低于华法林。NOAC 胃肠道出血和所有主要出血风险低于华法林的优势归因于非酒精性或非晚期肝硬化的亚组患者。
在亚洲患有非瓣膜性心房颤动的肝硬化患者中，NOAC 具有与华法林相当的血栓栓塞风险，且大出血风险较低。因此，对于此类患者，可以考虑使用低剂量的 NOAC 进行血栓预防。
